Sleep in schizophrenia: impairments, correlates, and treatment.

In untreated schizophrenia, psychotic decompensation is associated with profound insomnia, one of the prodromal symptoms associated with psychotic relapse. First- and second-generation antipsychotic medication can ameliorate this insomnia, but side effects may include sedation or residual insomnia. Patients who are clinically stable and medicated may continue to experience disturbed sleep, including long sleep-onset latencies, poor sleep efficiency, slow wave sleep deficits, and short rapid eye movement latencies. Schizophrenia also can be associated with comorbid sleep disorders, which may be enhanced or induced by antipsychotic medication. Sleep disorders in schizophrenia should be treated vigorously because normalized sleep and its restorative processes may be essential for a positive clinical outcome.     

An association between both low and high birth weight and increased disorganized and negative symptom severity in schizophrenia and other psychoses

Longitudinal cohort studies have implicated an association between both low and high birth weight and increased schizophrenia risk. In this study, we investigated the effect of birth weight on the symptom severity of psychotic disorders including schizophrenia in a Finnish schizophrenia family study sample. We used a multivariate GEE (General Estimating Equation) regression model to investigate the association of birth weight and symptom severity in 282 subjects with a primary psychotic disorder, 178 of whom had a diagnosis of schizophrenia. The Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS) were used as a measure of symptom severity. Sex, place of birth and year of birth were adjusted for in the model. Both low and high birth weight were associated with more severe symptoms with respect to bizarre behaviour, affective flattening and attentional impairment. In addition, low birth weight was associated with more severe symptoms with respect to positive formal thought. Our findings suggest that both low and high birth weight can influence the symptom severity of psychotic disorders. Our results implicate an association between both low and high birth weight and disorganized and negative symptoms.     

Usefulness of mindfulness-based cognitive therapy for treating insomnia in patients with anxiety disorders: a pilot study

The objective of this study was to examine the usefulness of a mindfulness-based cognitive therapy (MBCT) for treating insomnia symptoms in patients with anxiety disorder. Nineteen patients with anxiety disorder were assigned to an 8-week MBCT clinical trial. Participants showed significant improvement in Pittsburgh Sleep Quality Index (Z = -3.46, p = 0.00), Penn State Worry Questionnaire (Z = -3.83, p = 0.00), Ruminative Response Scale (Z = -3.83, p = 0.00), Hamilton Anxiety Rating Scale (Z = -3.73, p = 0.00), and Hamilton Depression Rating Scale scores (Z = -3.06, p = 0.00) at the end of the 8-week program as compared with baseline. Multiple regression analysis showed that baseline Penn State Worry Questionnaire scores were associated with baseline Pittsburgh Sleep Quality Index scores. These findings suggest that MBCT can be effective at relieving insomnia symptoms by reducing worry associated sleep disturbances in patients with anxiety disorder. However, well-designed, randomized, controlled trials are needed to confirm our findings.     

Symptom factors in early-onset psychotic disorders

OBJECTIVE: To examine the factor structure of symptom ratings in early-onset psychotic illnesses. METHOD: Subjects were drawn from a 2-year prospective study of early onset psychotic disorders. Principal components analysis with orthogonal (varimax) rotation was used to create factors from baseline ratings on the Schedule for Positive Symptoms, the Schedule for Negative Symptoms, and the Brief Psychiatric Rating Scale for Children. RESULTS: Youths with schizophrenia (n = 27), bipolar disorder (n = 22), and psychosis not otherwise specified (n = 20) were included. Four symptom factors were identified: negative symptoms, positive symptoms, behavioral problems, and dysphoria. Negative symptoms were predictive of the diagnosis of schizophrenia and treatment with antipsychotic medications. Neither behavior problems nor dysphoria were predictive of diagnosis. In subjects who completed follow-up assessments at year 1 (n = 49) and year 2 (n = 39), negative symptoms and behavioral problems predicted poorer functioning. CONCLUSIONS: The four factors are clinically relevant, with both treatment planning and prognostic implications. Negative symptoms best differentiated schizophrenia from the other disorders. Behavior problems and dysphoria were nonspecific problems that occurred in all three disorders, which likely leads to misdiagnosis in community settings.     

Do maternal psychotic symptoms predict offspring's psychotic disorder? Findings from the Helsinki High-Risk Study

The Helsinki High-Risk (HR) Study is a follow-up study of 179 offspring born to mothers with DSM-IV-TR diagnoses of schizophrenia, schizoaffective disorder, other schizophrenia spectrum disorders, and affective psychoses. Mothers comprised all female patients born between 1916 and 1948 who had been treated with hospital diagnoses of schizophrenia, schizophreniform, or schizoaffective psychoses in any mental hospital in the city of Helsinki up to 1974, and who had given birth in Helsinki between 1960 and 1964. In this report we conducted a principal factor analysis of maternal symptoms using 12 items of the Major Symptoms of Schizophrenia Scale (MSSS), the global ratings of anhedonia-asociality and avolition-apathy from the Scale for the Assessment of Negative Symptoms (SANS), and the global rating of bizarre behavior from the Scale for the Assessment of Positive symptoms (SAPS), and examined whether the factor scores predicted the offspring's morbidity from psychotic disorders. We found a four-factor solution (negative, positive, catatonic, and affective symptom factors). High maternal positive symptom factor score significantly predicted decreased morbidity from schizophrenia among offspring (P=0.0098). Our result suggests that maternal positive symptoms are less harmful to the child than other maternal psychotic symptoms, and supports the view that positive symptoms are non-specific symptoms of psychosis rather than core features of schizophrenia.     

Do the obsessive-compulsive symptoms have an effect in schizophrenia?

Objective

Schizophrenia presents with different symptom domains and functionality during its course. Obsessive-compulsive (OC) symptoms in schizophrenia have many themes to be clarified. Our aim was to compare schizophrenia patients with and without OC symptoms in terms of symptom domains, cognitive functions, and quality of life.

Method

Sixty-two patients who met schizophrenia diagnosis were assessed with Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition consecutively over a period of 12 months in the setting of an outpatient clinic at medical university hospital. Yale-Brown Obsessive-Compulsive Scale, Scale for the Assessment of Negative Symptoms, Scale for the Assessment of Positive Symptoms, and neuropsychologic tests were used. Quality of life was assessed with Quality of Life Scale for Patients with Schizophrenia.

Results

Obsessive-compulsive symptoms along with schizophrenia were present in a considerable number in our sample (35.5%). Level of psychotic symptoms was more severe and quality of life was lower in schizophrenia patients with OC symptoms. A positive correlation was found between obsessions and delusions. Moreover, there was a positive correlation between compulsions and total Scale for the Assessment of Positive Symptoms score and bizarre behaviors subscore. There was no difference between the 2 groups regarding neurocognitive functions. The level of quality of life of schizophrenic patients with OC symptoms was lower. Besides, no correlation was found between OC symptoms and neurocognition and quality of life.

Conclusions

The findings of this study indicate that schizophrenia patients with OC symptoms had severe psychotic symptoms with a distinctive clinical picture including good neurocognition but poor functioning.     

Treatment adherence and quality of sleep in schizophrenia outpatients

Objective. Patients with schizophrenia (SZ) often present sleep complaints, and patients with sleep disturbances are at a greater risk for symptom worsening after antipsychotic discontinuation. Long-term adherence to antipsychotic treatment remains a challenge for clinicians, and the relationship between quality of sleep and treatment adherence in SZ outpatients has been poorly studied. Methods. In this cross-sectional, non-interventional study, 811 adult outpatients with a diagnosis of SZ were divided into two groups according to the presence (or absence) of sleep disturbances, and assessed using measures of symptom severity, quality and patterns of sleep, adherence/compliance to treatment, and family support degree. Results. Patients with sleep disturbances were significantly more symptomatic (p < 0.0001), and scored significantly higher on the Pittsburgh Sleep Quality Index (PSQI) as compared with patients without sleep disturbances (p < 0.0001). More compliant patients showed less sleep disturbances (p < 0.0001); moreover, patients with worse compliance to pharmacological treatment showed significantly higher scores on the PSQI (p < 0.0001). Regarding family support degree, patients with sleep disorders presented a lower family support (p = 0.0236), and patients with worse treatment adherence had worse family support (p < 0.0001). Conclusions. Our findings show that SZ outpatients reporting sleep disturbances show greater symptom severity, and worse adherence/compliance to treatment, as well as a lower family support.     

Schizophrenic relapse after drug withdrawal is predictable

Thirty-two patients in remission were followed by regular ratings during a prospective neuroleptic withdrawal study. They were outpatients who fulfilled the DSM-III criteria of schizophrenia and who were motivated for drug withdrawal. The relapse rate was 81%. The results from the rating scales confirm the hypothesis that a symptom increase occurs before psychotic relapse. In the order statistical differences occurred, the factors predicting relapse were those concerned with positive psychopathology, motor dysfunction, impaired affects and sleep disturbances. The corresponding symptoms and signs were mainly concerned with thought disorders, paranoid ideation, overactivity, depression and insomnia middle, all of nonpsychotic degree of severity. If prodromes appear, the patient should resume his neuroleptic treatment, or other preventive measures should be taken. By such therapeutic interactions, psychotic relapse may be prevented, or can be dealt with in an outpatient setting.     

Responses to antipsychotic therapy among patients with schizophrenia or schizoaffective disorder and either predominant or prominent negative symptoms

Patients with schizophrenia who have predominant negative symptoms are often considered less responsive to treatment. This analysis of patients with schizophrenia or schizoaffective disorder compares changes in symptom severity between those with predominant versus merely prominent negative symptoms. Prominent negative symptoms were defined by a baseline score of ≥4 on at least 3, or ≥5 on at least 2, of the 7 Positive and Negative Syndrome Scale (PANSS) negative subscale items. Predominant negative symptoms were defined by the foregoing plus a PANSS positive score of <19, a Barnes Akathisia score of <2, a Simpson-Angus score of <4, and a Calgary Depressive Scale score of <9. Adult patients with schizophrenia (n=227) or schizoaffective disorder (n=116) received either olanzapine (10-20mg/day, n=169) or quetiapine (300-700mg/day, n=174) for up to 24weeks. Data for both medications were pooled. Of the 343 patients enrolled in the study, 34.7% met the criteria for predominant negative symptoms, the remaining 65.3% being characterized only by their prominent negative symptoms. Changes in the severity of negative symptoms in both patient types largely followed similar trajectories during treatment, as reflected both in Marder PANSS negative subscale scores and in the Scale for Assessment of Negative Symptoms total and domain scores. Patients with either predominant or prominent negative symptoms therefore appear to respond similarly to atypical antipsychotic treatment. This distinction, incorporating an evaluation of the presence of positive, affective, and extrapyramidal symptoms, may therefore not have prognostic implications for the responsiveness of patients' negative symptoms to treatment.     

Social anxiety in outpatients with schizophrenia: a relevant cause of disability

OBJECTIVE: Social anxiety is a frequent but often unrecognized feature in schizophrenia and is associated with a severe level of disability. To precisely define the assessment, impact, clinical correlates, and consequences of social anxiety in schizophrenia, the authors conducted a survey of schizophrenia patients and a comparison cohort of patients with social anxiety disorder. METHOD: A consecutively enrolled group of 80 outpatients with DSM-IV schizophrenia and a consecutive comparison group of 27 patients with social anxiety disorder were recruited from an institutional psychiatric practice and assessed with the Liebowitz Social Anxiety Scale, Scale for the Assessment of Negative Symptoms, Scale for the Assessment of Positive Symptoms, Social Adjustment Scale, and the Medical Outcomes Study 36-item Short-Form Health Survey. RESULTS: Social anxiety scores of schizophrenia patients with comorbid social anxiety disorder (N=29, 36.3%) did not differ from those of subjects with social anxiety disorder as their primary diagnosis. Schizophrenia patients without social anxiety disorder had significantly lower total scores on the Liebowitz Social Anxiety Scale and lower social and performance anxiety subscale scores than did the other two groups. No differences in negative and positive symptom rates were found between schizophrenia patients with and without social anxiety disorder. Schizophrenia patients with social anxiety disorder had a higher lifetime rate of suicide attempts, greater lethality of suicide attempts, more past substance/alcohol abuse disorder, lower social adjustment, and lower overall quality of life. CONCLUSIONS: Social anxiety is a highly prevalent, disabling condition in outpatients with schizophrenia that is unrelated to clinical psychotic symptoms. The Liebowitz Social Anxiety Scale appeared adequate and reliable in assessing social anxiety disorder in patients with schizophrenia. If these data are confirmed, this study will make a contribution to the search for operational guidelines and adequate next-step treatments for social anxiety disorder in schizophrenia patients.     

The factor structure for positive and negative symptoms in South African Xhosa patients with schizophrenia

Most studies investigating the symptom dimensions of schizophrenia utilising the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) favour a three factor model. This study sought to investigate the factor structure of both the global and individual items of the SANS and SAPS in a large sample of South African Xhosa patients with schizophrenia. A total of 422 subjects participated. Both principal components and factor analytical procedures were applied. For the global items, a two-factor solution representing positive and negative symptoms accounted for 59.9% of the variance. Alternatively, the three-dimensional model of negative, psychotic and disorganisation factors was supported by a five-factor solution if the more heterogeneous items of attention and alogia were ignored. Analysis of the individual items yielded a five-factor solution with the negative symptoms splitting into diminished expression and disordered relating, and the positive symptoms separating into factors for psychosis, thought disorder and bizarre behaviour. Our findings are very similar to those from other parts of the world, providing evidence that the factor structure for the symptoms of schizophrenia is relatively resistant to cultural influences. This is particularly true for negative symptoms.     

Influence of ZNF804a on Brain Structure Volumes and Symptom Severity in Individuals With Schizophrenia

CONTEXT The single-nucleotide polymorphism rs1344706 in the gene ZNF804a has been associated with schizophrenia and with quantitative phenotypic features, including brain structure volume and the core symptoms of schizophrenia. OBJECTIVE To evaluate associations of rs1344706 with brain structure and the core symptoms of schizophrenia. DESIGN Case-control analysis of covariance. SETTING University-based research hospital. PARTICIPANTS Volunteer sample of 335 individuals with schizophrenia spectrum disorders (306 with core schizophrenia) and 198 healthy volunteers. MAIN OUTCOME MEASURES Cerebral cortical gray matter and white matter (WM) volumes (total and frontal, parietal, temporal, and occipital lobes), lateral ventricular cerebrospinal fluid volume, and symptom severity from the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms divided into 3 domains: psychotic, negative, and disorganized. RESULTS The rs1344706 genotype produced significant main effects on total, frontal, and parietal lobe WM volumes (F =?3.98, P?=?.02; F =?4.95, P?=?.007; and F =?3.08, P?=?.05, respectively). In the schizophrenia group, rs1344706 produced significant simple effects on total (F =?3.93, P?=?.02) and frontal WM volumes (F =?7.16, P?<?.001) and on psychotic symptom severity (F =?6.07, P?=?.003); the pattern of effects was concordant with risk allele carriers having larger volumes and more severe symptoms of disease than nonrisk homozygotes. In the healthy volunteer group, risk allele homozygotes had increased total WM volume compared with nonrisk allele carriers (F =?4.61, P?=?.03), replicating a previously reported association. CONCLUSIONS A growing body of evidence suggests that the risk allele of rs1347706 is associated with a distinctive set of phenotypic features in healthy volunteers and individuals with schizophrenia. Our study supports this assertion by finding that specific genotypes of the polymorphism are associated with brain structure volumes in individuals with schizophrenia and healthy volunteers and with symptom severity in schizophrenia.     

Heterocyclic antidepressant, monoamine oxidase inhibitor and neuroleptic withdrawal phenomena

1. The authors review the literature describing acute symptomatology produced by the gradual or abrupt withdrawal of heterocyclic antidepressants, monoamine oxidase inhibitors (MAOI) and neuroleptics. 2. Withdrawal of heterocyclic antidepressants and antipsychotic agents causes similar symptomatology. Symptoms produced by the discontinuation of these drugs include nausea, emesis, anorexia, diarrhea, rhinorrhea, diaphoresis, myalgias, paresthesias, anxiety, agitation, restlessness, and insomnia. 3. Psychotic relapse is often presaged by anxiety, agitation, restlessness, and insomnia. Prodromal symptoms are distinguished from the effects of neuroleptic withdrawal by a temporal relationship of the latter to reductions in the dosage or discontinuation of antipsychotic agents. 4. Withdrawal of MAOIs can result in severe anxiety, agitation, pressured speech, sleeplessness or drowsiness, hallucinations, delirium, and paranoid psychosis. 5. MAOI withdrawal phenomena resemble the symptoms produced by the discontinuation of chronically administered psychostimulants. 6. The capacity of MAOIs to exert amphetamine-like effects presynaptically and the propensity of somatic treatments for depression to subsensitize presynaptic receptors regulating the release of catecholamines provide a basis for the development of psychotic symptoms upon the withdrawal of MAOI. Evidence for this hypothesis is reviewed.     

Effects of changing from typical to atypical antipsychotic drugs on subjective sleep quality in patients with schizophrenia in a Japanese population

OBJECTIVE: To investigate the effects of the atypical antipsychotic drugs risperidone, olanzapine, quetiapine, and perospirone on the subjective quality of sleep in patients with schizophrenia. METHOD: Subjects were 92 inpatients (mean age = 59.9 years) who had been receiving treatment with conventional antipsychotic drugs and who met the DSM-IV criteria for schizophrenia. Subjects were randomly assigned to receive 1 of 4 atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, and risperidone). Subjective sleep quality and psychopathology were assessed twice: at baseline and 8 weeks after switching. Data were collected from June 2001 to December 2001. Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), and psychopathology was measured by the Positive and Negative Syndrome Scale (PANSS). RESULTS: Subjective sleep quality as assessed by the PSQI was significantly improved with administration of olanzapine, risperidone, or quetiapine, but not with perospirone, in comparison with conventional antipsychotic drugs. Multiple regression analysis revealed that the improvement of sleep quality with administration of atypical antipsychotic drugs was predicted by poor sleep quality at baseline. In addition, improvement of sleep quality was significantly correlated with improvement of negative symptoms as assessed by the PANSS. CONCLUSION: These results demonstrated that atypical antipsychotic drugs improved subjective quality of sleep in patients with schizophrenia compared with conventional antipsychotic drugs, suggesting that the marked potency of serotonin-2 receptor blockade in atypical antipsychotic drugs may be involved in the mechanism of this improvement. These improvements were correlated with improvement of negative symptoms.     

Differential effects of childhood abuse and neglect: mediation by posttraumatic distress in neurotic disorder and negative symptoms in schizophrenia?

Dissociation, though understood as a response to trauma, lacks a proven etiology. The assumption of a dose-response relationship between trauma, dissociation and Schneiderian symptoms led to the proposal of a dissociative subtype of schizophrenia characterized by severe child maltreatment, dissociation and psychosis. Child maltreatment and dissociation are common features of neurotic disorders as well, and the link between trauma, dissociation, and hallucinations is not specific for schizophrenia. This study compares childhood abuse and neglect, posttraumatic distress and adult dissociation in patients with psychotic vs. non-psychotic disorder. Thirty-five participants with non-psychotic disorder and twenty-five with schizophrenia were analyzed using the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), the Montgomery-Åsberg Depression Rating Scale (MADRS), the Posttraumatic Stress Diagnostic Scale PDS (PDS), the Childhood Trauma Questionnaire (CTO) and the Arbeitsgemeinschaft Methodik und Dokumentation in der Psychiatrie (AMDP)-module on dissociation. Trauma and clinical syndromes were compared by means of T-testing and logistic regression between 1) the diagnoses and 2) groups with and without post-traumatic stress disorder (PTSD), marked dissociation and psychotic symptoms. While non-psychotic disorder was related to abuse, schizophrenia showed an association with neglect. Childhood trauma predicted posttraumatic symptomatology and negative symptoms. Childhood abuse and neglect may effectuate different outcomes in neurotic and psychotic disorder. The underlying mechanisms, including dissociation, dovetail with cognitive, emotional and behavioural changes involved in depression, posttraumatic distress and chronic schizophrenia symptoms rather than being directly linked to trauma.     

The influence of personality and dysfunctional sleep-related cognitions on the severity of insomnia

Previous findings suggest that personality traits and dysfunctional sleep-related cognitions may perpetuate insomnia, but findings concerning this have been scarce. Thus, we hypothesized that personality and sleep-related cognitions influence the severity of insomnia, and investigated the association personality and sleep-related cognitions had with various sleep-related parameters, including severity of insomnia. Forty-four patients with psychophysiological insomnia were assessed using The Temperament and Character Inventory, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Dysfunctional Belief and Attitudes toward Sleep Scale, the Pre-Sleep Arousal Scale and the Hospital Anxiety and Depression Scale. Insomnia severity was significantly and positively correlated with harm avoidance, self-transcendence and sleep-related cognitions, and negatively correlated with novelty seeking, reward dependence, and cooperativeness. Dysfunctional sleep-related cognitions were positively correlated with insomnia severity and sleep quality. Stepwise multiple regression analysis showed that sleep-related cognitions, depression and reward dependence scores were significant determinants of insomnia severity, and that sleep-related cognitions and self-transcendence were significant positive determinants of sleep quality. Reward dependence, depression and sleep-related cognitions were associated with insomnia severity, and comparison with previous findings implied that 'internalizing behavior' and depression may be more plausible candidates for the link between personality and insomnia than anxiety. Considering the major role of cognitive-behavioral treatment (CBT) in the treatment of insomnia, assessment of these factors and management of sleep-related cognitions may help alleviate symptoms in patients with insomnia.     

长期抗精神病药治疗撤药时的运动障碍

目的：调查撤药出现的运动障碍（ＷＥ－Ｄ）是否为迟发性运动障碍（ＴＤ）的早期征象。方法：７１例精神分裂症病人停药２周,于停药前及停药后第２周末评定迟发性运动障碍量表（Ｓｉｍｐ－ｓｏｎ量表）及阴性症状量表,收集临床资料,并随访半年。结果：无ＴＤ组病人年龄、病程显著低于ＷＥ－Ｄ组及ＴＤ组病人;ＷＥ－Ｄ组与ＴＤ组病人间年龄、病程、抗精神病药治疗持续时间、平均剂量及阴性症状间无显著差异。结论：ＷＥ－Ｄ可能是ＴＤ的一个早期表现或为一隐匿性运动障碍     

The entorhinal cortex in first-episode psychotic disorders: a structural magnetic resonance imaging study

OBJECTIVE: Neuropathological findings regarding the entorhinal cortex in schizophrenia are conflicting. The authors used structural magnetic resonance imaging to examine the entorhinal cortex volumes of healthy subjects and medication-naive patients experiencing their first episode of psychotic illness. METHOD: The study included 33 patients with schizophrenia and related disorders, 11 patients with nonschizophrenic disorders, and 43 matched healthy subjects. All subjects were rated on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, and volumetric measurements of the entorhinal cortex were obtained for all subjects. The authors examined differences across the groups as well as clinical correlations of entorhinal cortex volumes adjusted for intracranial volume. RESULTS: A significant diagnosis effect was seen in the left entorhinal cortex: patients with schizophrenia and related disorders and patients with nonschizophrenic psychotic disorders had smaller left entorhinal cortex volumes than healthy subjects. The mean entorhinal cortex volume of patients with schizophrenic disorders did not differ from that of patients with nonschizophrenic psychotic disorders. In patients with schizophrenic disorders, the entorhinal cortex volume positively correlated with severity of delusions. The mean entorhinal cortex volume of patients with nondelusional psychotic disorders was significantly smaller than that of patients with delusional psychotic disorders and healthy subjects. CONCLUSIONS: Smaller entorhinal cortex volume in first-episode, neuroleptic-naive psychotic disorders may not be a confound of the effects of illness chronicity or antipsychotic treatment. Entorhinal cortex pathology appears to have a significant association with positive symptoms, specifically delusions. The impairment of functions in which the entorhinal cortex participates-such as novelty detection, associative learning, and processing episodic, recognition, and autobiographical memory-could be responsible for its association with psychotic disorders and delusions.     

Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel nonbenzodiazepine hypnotic. Zaleplon Clinical Study Group.

BACKGROUND: Zaleplon is a short-acting pyrazolopyrimidine hypnotic with a rapid onset of action. This multicenter study compared the efficacy and safety of 3 doses of zaleplon with those of placebo in outpatients with DSM-III-R insomnia. Zolpidem, 10 mg, was used as an active comparator. METHOD: After a 7-night placebo (baseline) period, 615 adult patients were randomly assigned to receive, in double-blind fashion, I of 5 treatments (zaleplon, 5, 10, or 20 mg; zolpidem, 10 mg; or placebo) for 28 nights, followed by placebo treatment for 3 nights. Sleep latency, sleep maintenance, and sleep quality were determined from sleep questionnaires that patients completed each morning. The occurrence of rebound insomnia and withdrawal effects on discontinuation of treatment was also assessed. All levels of significance were p < or = .05. RESULTS: Median sleep latency was significantly lower with zaleplon, 10 and 20 mg, than with placebo during all 4 weeks of treatment and with zaleplon, 5 mg, for the first 3 weeks. Zaleplon, 20 mg, also significantly increased sleep duration compared with placebo in all but week 3 of the study. There was no evidence of rebound insomnia or withdrawal symptoms after discontinuation of 4 weeks of zaleplon treatment. Zolpidem, 10 mg, significantly decreased sleep latency, increased sleep duration, and improved sleep quality at most timepoints compared with placebo; however, after discontinuation of zolpidem treatment, the incidence of withdrawal symptoms was significantly greater than that with placebo and there was an indication of significant rebound insomnia for some patients in the zolpidem group compared with those in the placebo group. The frequency of adverse events in the active treatment groups did not differ significantly from that in the placebo group. CONCLUSION: Zaleplon is effective in the treatment of insomnia. In addition, zaleplon appears to provide a favorable safety profile, as indicated by the absence of rebound insomnia and withdrawal symptoms once treatment was discontinued.